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Anticancer Agent α-sulfoquinovosyl-acylpropanediol Enhances the Radiosensitivity of Human Malignant Mesothelioma in Nude Mouse Models

Overview

Overview

Journal J Radiat Res

Publisher Oxford University Press

Specialties Environmental Health
Oncology
Radiology

Date 2021 Nov 5

PMID 34738103

Authors

Authors

Eiko Inamasu

Tomoshi Tsuchiya

Motohiro Yamauchi

Kodai Nishi

Katsuya Matsuda

Fumio Sugawara

Kengo Sakaguchi

Ryoichi Mori

Keitaro Matsumoto

Takuro Miyazaki

Go Hatachi

Ryoichiro Doi

Hironosuke Watanabe

Koichi Tomoshige

Naoki Matsuda

Yoshikazu Higami

Isao Shimokawa

Masahiro Nakashima

Takeshi Nagayasu

Affiliations

Affiliations

Soon will be listed here.

Abstract

Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P = 0.0127) and the radiation treatment alone (P = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models.

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